When animals are chronically exposed to different trace metals, each metal produces an enzymatic response profile which specifically characterizes exposure to that metal. It is the objective of these studies to assess and characterize response profiles resulting from exposure to various environmentally important toxic metals and to apply knowledge of their response profiles to the design of tests (such as the ALA test currently available for the detection of lead) for use among human populations in detecting pre-clinical, i.e., pre-toxic, exposure to a given metal. Specific metals and areas of interest include the biochemical effects of methyl mercury, arsenic, lead, and lead plus fluoride on mitochondrial structure and function. Enzyme activities associated with mitochondrial membranes have been found to show early and pronounced changes in mitochondria of rats and mice following chronic exposure to methyl mercury and arsenic. Further development of these biochemical response profiles should permit development of metal-specific biochemical testing procedures which accurately assess a biological response to exposure from these agents.